Pax6 controls centriole maturation in cortical progenitors through Odf2.

Tylkowski, M. A.; Yang, K.; Hoyer-Fender, S.; Stoykova, A.

doi:10.1007/s00018-014-1766-1

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Pax6 controls centriole maturation in cortical progenitors through Odf2.

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Tylkowski, M. A.
Research Group of Molecular Developmental Neurobiology, MPI for Biophysical Chemistry, Max Planck Society;

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Stoykova, A.
Research Group of Molecular Developmental Neurobiology, MPI for Biophysical Chemistry, Max Planck Society;

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Citation

Tylkowski, M. A., Yang, K., Hoyer-Fender, S., & Stoykova, A. (2015). Pax6 controls centriole maturation in cortical progenitors through Odf2. Cellular and Molecular Life Sciences, 72(9), 1795-1809. doi:10.1007/s00018-014-1766-1.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0024-3ED7-0

Abstract

Cortical glutamatergic neurons are generated by radial glial cells (RGCs), specified by the expression of transcription factor (TF) Pax6, in the germinative zones of the dorsal telencephalon. Here, we demonstrate that Pax6 regulates the structural assembly of the interphase centrosomes. In the cortex of the Pax6-deficient Small eye (Sey/Sey) mutant, we find a defect of the appendages of the mother centrioles, indicating incomplete centrosome maturation. Consequently, RGCs fail to generate primary cilia, and instead of staying in the germinative zone for renewal, RGCs detach from the ventricular surface thus affecting the interkinetic nuclear migration and they exit prematurely from mitosis. Mechanistically, we show that TF Pax6 directly regulates the activity of the Odf2 gene encoding for the appendage-specific protein Odf2 with a role for the assembly of mother centriole. Our findings demonstrate a molecular mechanism that explains important characteristics of the centrosome disassembly and malfunctioning in developing cortex lacking Pax6.